Higo S. Disease modeling of desmosome-related cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes. World J Stem Cells 2023; 15(3): 71-82 [PMID: 37007457 DOI: 10.4252/wjsc.v15.i3.71]
Corresponding Author of This Article
Shuichiro Higo, MD, PhD, Specially Appointed Associate Professor, Department of Medical Therapeutics for Heart Failure, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan. higo-s@cardiology.med.osaka-u.ac.jp
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Mar 26, 2023; 15(3): 71-82 Published online Mar 26, 2023. doi: 10.4252/wjsc.v15.i3.71
Disease modeling of desmosome-related cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes
Shuichiro Higo
Shuichiro Higo, Department of Medical Therapeutics for Heart Failure, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
Author contributions: Higo S wrote the manuscript; the author has read and approved the final manuscript.
Supported byJSPS KAKENHI, No. 20K21602, No. 21H02915, and No. 22K19526; the Japan Agency for Medical Research and Development, No. 21bm0804008h0005; the Cell Science Research Foundation; the Grant for Basic Research of the Japanese Circulation Society (2018); and SENSHIN Medical Research Foundation.
Conflict-of-interest statement: Department of Medical Therapeutics for Heart Failure is a Joint Research Department with TOA EIYO Pharmaceutical Company. Dr. Higo reports grants from TOA EIYO Pharmaceutical Company, during the conduct of the study.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shuichiro Higo, MD, PhD, Specially Appointed Associate Professor, Department of Medical Therapeutics for Heart Failure, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan. higo-s@cardiology.med.osaka-u.ac.jp
Received: December 16, 2022 Peer-review started: December 16, 2022 First decision: February 3, 2023 Revised: February 10, 2023 Accepted: March 15, 2023 Article in press: March 15, 2023 Published online: March 26, 2023 Processing time: 97 Days and 1.1 Hours
Abstract
Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation. Although optimized medical therapies have been developed for heart failure during the last few decades, some patients with cardiomyopathy exhibit advanced heart failure and are refractory to medical therapies. Desmosome, which is a dynamic cell-to-cell junctional component, maintains the structural integrity of heart tissues. Genetic mutations in desmosomal genes cause arrhythmogenic cardiomyopathy (AC), a rare inheritable disease, and predispose patients to sudden cardiac death and heart failure. Recent advances in sequencing technologies have elucidated the genetic basis of cardiomyopathies and revealed that desmosome-related cardiomyopathy is concealed in broad cardiomyopathies. Among desmosomal genes, mutations in PKP2 (which encodes PKP2) are most frequently identified in patients with AC. PKP2 deficiency causes various pathological cardiac phenotypes. Human cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPSCs) in combination with genome editing, which allows the precise arrangement of the targeted genome, are powerful experimental tools for studying disease. This review summarizes the current issues associated with practical medicine for advanced heart failure and the recent advances in disease modeling using iPSC-derived cardiomyocytes targeting desmosome-related cardiomyopathy caused by PKP2 deficiency.
Core Tip: Prevention of advanced heart failure caused by cardiomyopathy is an urgent unmet need in the field of cardiovascular medicine. Desmosome, a cell-to-cell junctional component, maintains the structural integrity of heart tissues. Genetic mutations in desmosomal genes cause desmosome-related cardiomyopathy, an intractable disease refractory to standard medical therapies. This review introduces the recent advances in disease modeling of desmosome-related cardiomyopathy caused by PKP2 mutations using induced pluripotent stem cell-derived cardiomyocytes.
